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N-acetylcysteine in Intra-amniotic Infection/Inflammation

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ClinicalTrials.gov Identifier: NCT00397735
Recruitment Status : Completed
First Posted : November 9, 2006
Last Update Posted : October 10, 2018
Sponsor:
Information provided by (Responsible Party):
Catalin S Buhimschi, MD, Ohio State University

November 7, 2006
November 9, 2006
October 10, 2018
October 1, 2006
October 29, 2012   (Final data collection date for primary outcome measure)
composite of mortality and severe short term neonatal morbidities (IVH, NEC, BPD, ROP, sepsis, newborn death) [ Time Frame: up to 1 year ]
IVH, NEC, BPD, ROP, Sepsis, death
  • neonatal death
  • early onset neonatal sepsis
Complete list of historical versions of study NCT00397735 on ClinicalTrials.gov Archive Site
  • neonatal sepsis [ Time Frame: up to 30 days ]
    early and late neonatal sepsis
  • maternal and umbilical cord plasma antioxidant capacity [ Time Frame: up to 1 day ]
    plasma antioxidant capacity
  • maternal and umbilical cord plasma N-acetylcysteine levels [ Time Frame: up to 1 day ]
    N-acetylcysteine levels
  • umbilical cord levels of inflammatory cytokine concentrations [ Time Frame: up to 1 day ]
    pannel of pro and anti inflammatory cytokines
  • funisitis grades [ Time Frame: up to 1 day ]
    histology
  • maternal and umbilical cord blood glutathione concentration [ Time Frame: up to 1 day ]
    glutathione levels
  • maternal and umbilical cord plasma N-acetylcysteine levels
  • maternal and umbilical cord plasma antioxidant capacity
  • maternal and umbilical cord blood glutathione concentration
  • umbilical cord levels of inflammatory cytokine concentrations
  • funisitis grades
  • other neonatal outcomes (respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, retinopathy of prematurity, late-onset sepsis, bronchopulmonary dysplasia)
Not Provided
Not Provided
 
N-acetylcysteine in Intra-amniotic Infection/Inflammation
Effect of N-acetylcysteine in Preventing Adverse Neonatal Outcomes in Women With Intra-amniotic Infection/Inflammation
The aim of the study is to determine if N-acetylcysteine (a potent free radical scavenger) prevents the occurrence of adverse neonatal outcomes in preterm deliveries complicated by infection associated with preterm labor or preterm premature rupture of membranes (PPROM). The working hypothesis is that in pregnancies complicated by intra-amniotic infection or inflammation, N-acetylcysteine protects the fetus by preventing the development, or decreasing the intensity and/or progression of the fetal inflammatory syndrome.

Despite extensive research, the etiology of most preterm births remains unknown. There are significant fetal consequences associated with preterm birth, which include necrotizing enterocolitis, fetal respiratory distress and intra-ventricular hemorrhage. Perinatal mortality is about 44%, 11% and 5% when deliveries occur between 25-28 weeks, 29-32 weeks and 33-34 weeks, respectively. While for many years, it was assumed that the cause of the high morbidity associated with prematurity was the birth of a neonate with a restricted adaptive capacity, it has also been suggested that part of the high perinatal morbidity was the consequence of adverse processes affecting the fetus in utero, rather than of prematurity per se. Intra-amniotic inflammation present in utero early in gestation may trigger the cascade of events leading to preterm birth (i.e. rupture of membranes, cervical ripening, uterine contractions) and provide an intrauterine milieu which is unfavorable or even harmful to the fetus.

Most living organisms have developed well-integrated, antioxidant defenses to scavenge free radicals and control their intracellular concentration. A loss of balance between free radicals and antioxidants (the redox balance) is one mechanism of cell injury in diseases associated with inflammation. N-acetylcysteine is an approved anti-oxidant medication drug used during pregnancy for treatment of mothers with acetaminophen (Tylenol) toxicity. N-acetylcysteine has been safely administered during pregnancy in over 100 women who overdosed with Tylenol and to preterm and healthy term newborns for other purposes. It is a goal of our trial to prevent free radical formation by administering N-acetylcysteine and to further study whether the outcome of preterm deliveries will improve compared to a control group which will not receive placebo infusion

Interventional
Phase 1
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Labor, Premature
  • Preterm Premature Rupture of the Membranes
  • Infection
  • Inflammation
  • Chorioamnionitis
  • Procedure: amniocentesis
    Amniotic fluid will be retrieved for routine amniocentesis to rule-out or confirm intra-amniotic infection and /or inflammation. The amniocentesis procedure will be clinically indicated and the patient will undergo the procedure independent of our study.
    Other Name: transabdominal amniocentesis
  • Drug: N-acetylcysteine or placebo
    Only women with amniocentesis results consistent with infection/inflammation will be randomized
    Other Names:
    • Mucomyst
    • Acetadote
  • Experimental: N-Acetylcysteine
    The subjects enrolled in our research protocol must have evidence of infection/inflammation at amniocentesis in order to receive N-acetylcysteine. Women with positive amniocentesis results The dose of N-acetylcysteine is the one recommended to be used in humans to prevent acetaminophen toxicity: 150 mg/kg loading dose (60 min), followed by 50mg/kg IV continuous infusion rate for 4 hours, and followed by 100 mg/kg IV continuous infusion rate for the following 16 hours. Acetadote (Cumberland Pharmaceuticals) is the only FDA-approved intravenous N-acetylcysteine formulation and will be used in our study.
    Interventions:
    • Procedure: amniocentesis
    • Drug: N-acetylcysteine or placebo
  • Placebo Comparator: Placebo
    The subjects enrolled in our research protocol must have infection/inflammation in order to be randomized to receive N-acetylcysteine or placebo. Placebo-assigned patients will receive sodium chloride solution without N-acetylcysteine
    Interventions:
    • Procedure: amniocentesis
    • Drug: N-acetylcysteine or placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
68
100
August 1, 2018
October 29, 2012   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Women admitted onto the Labor and Birth Ward or Maternal Special Care Units of the Yale New Haven Hospital who have a clinically indicated amniocentesis which demonstrates presence of intra-amniotic infection and/or inflammation.

Exclusion Criteria:

  • Patients that require immediate intervention or close medical supervision (cardiac and renal disease, congestive heart failure, history of asthma), maternal infection (HIV, hepatitis B or C), cord prolapse, known fetal malformation, allergic reactions to N-acetylcysteine, preeclampsia
Sexes Eligible for Study: Female
18 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00397735
0603001228
No
Not Provided
Not Provided
Catalin S Buhimschi, MD, Ohio State University
Ohio State University
Not Provided
Principal Investigator: Catalin S Buhimschi, MD, MBA Ohio State University
Ohio State University
October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP